Triple-negative breast cancer (TNBC), while sensitive to chemotherapy, remains a challenge due to its differential response to treatment and poor prognosis. In a population of TNBC patients treated with NACT with docetaxel plus carboplatin (TCb), we evaluated the predictive value of the intrinsic subtype by PAM50.
Pathological response was defined by RCB (residual cancer burden) method, with pathological complete response (pCR) considered as lack of invasive tumor in breast plus axilla (ypT0/isypN0). Intrinsic subtype was determined by PAM50 gene expression assay using the nCounter platform (nanoString Technologies Inc; Seattle, USA). Association between RCB and subtypes was assessed on R software.
121 consecutive patients received NACT with TCb in a prospective multicenter trial, 95 were available for the PAM50 analysis. Overall, the distribution of responses was: pCR 44%, class I 13%, class II 31%, and class III 14%. The majority of the tumors were basal-like (BL) (83%), followed by HER2E (13%), normal-like (3%) and luminal B (1%). A clear difference between the intrinsic subtypes with regard to RCB distribution was found (p = 0.009, Table 1). BL tumors had a significantly better response to TCb: 51 % achieved pCRvs 13% of non-BL tumors (p = 0.0055). Multivariate analyses including tumor size and nodal status confirmed the significance of intrinsic subtype for the prediction of response. Concordantly, resistance to TCb was more frequent in non-BL tumors (38% RCB-II, 31% RCB-III) as compared to BL (29 % and 10%).
RCB distribution across subtypes (Symmans et al, JCO 2007)
|%||All (n = 95)||Basal-like (n = 79)||Non-Basal (n = 16)|
TCb was shown to be an effective NACT regimen for TNBC with a pCR rate of 44%. Intrinsic subtype by PAM50 helps predict response to NACT with TCb, with BL TNBC associated with significant better outcomes as compared to non-BL TNBC (pCR rates of 51 % vs 13% respectively, p 0.0051), although better predictors of response are still needed.
Clinical trial identification
Legal entity responsible for the study
Instituto de Investigacion Sanitaria Gregorio Marañon, Universidad Complutense, Madrid
This work was partially supported by the Ministry of Economy and Competitiveness ISCIII-FIS grants PI12/02684, and RD12/0036/0076, co-financed by ERDF (FEDER) Funds from the European Commission, “A way of making Europe”.
All authors have declared no conflicts of interest.